This is a 371 of international application PCT/EP00/05476 with international filing date Jun. 14, 2000.
The present invention relates to a new process for the preparation of herbicidally active substituted 3-hydroxy-4-aryl-5-oxopyrazoline derivatives.
3-Hydroxy-4-aryl-5-oxopyrazolines having herbicidal action and the preparation thereof are described, for example, in WO 92/16510, EP-A-0 508 126, WO 95/01971, WO 96/21652, WO 96/25395, WO 97/02243 and in WO 99/47525.
Surprisingly, it has now been found that substituted 3-hydroxy-4-aryl-5-oxopyrazoline derivatives can readily be prepared in a high yield and with a high degree of purity by the condensation of arylmalonic acid diamides or arylmalonic acid monoamides with hydrazine derivatives.
The present invention accordingly relates to a process for the preparation of compounds of formula I: 
wherein
R0 is, each independently of any other, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, cyano-C1-C6alkyl, C2-C6haloalkenyl, cyano-C2-C6alkenyl, C2-C6haloalkynyl, cyano-C2-C6alkynyl, hydroxy, hydroxy-C1-C6alkyl, C1-C6alkoxy, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylsulfonylamino, C1-C6alkylaminosulfonyl, C1-C6alkylcarbonyl, C1-C6alkylcarbonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl-C2-C6alkenyl, C1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or an aromatic ring that contains 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the latter two aromatic rings may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro; or
R0, together with the adjacent substituents R1, R2 and R3, forms a saturated or unsaturated C3-C6hydrocarbon bridge that may be interrupted by 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and/or may be substituted by C1-C4alkyl;
R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl, C2-C6haloalkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkylcarbonyl-C2-C6alkynyl, cyano-C2-C6alkynyl, nitro-C2-C6alkynyl, C3-C6halocycloalkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, C1-C6alkoxy-C1-C6alkoxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino or phenoxy in which the phenyl ring may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro;
R2 also may be phenyl, naphthyl or a 5- or 6-membered aromatic ring that may contain 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halogen, C3-C8cycloalkyl, hydroxy, mercapto, amino, cyano, nitro or by formyl; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl-(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or by C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halo-substituted C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl-(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl, mono- or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by a radical of the formula COOR50, CONR51, SO2NR53R54 or SO2OR55 wherein R50, R51, R52, R53, R54 and R55 are each independently of the others C1-C6alkyl, C2-C6alkenyl or C3-C6alkynyl or halo-, hydroxy-, alkoxy-, mercapto-, amino-, cyano-, nitro-, alkylthio-, alkylsulfinyl- or alkylsulfonyl-substituted C1-C6alkyl, C2-C6alkenyl or C3-C6alkynyl;
n is 0, 1 or 2;
R4 and R5 are each independently of the other hydrogen, C1-C12alkyl, C1-C12haloalkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C10alkoxy-C1-C8alkyl, poly-C1-C10alkoxy-C1-C8alkyl, C1-C10alkylthio-C1-C8alkyl, C3-C8cycloalkyl, C3-C8halocycloalkyl, 4- to 8-membered heterocyclyl, phenyl, xcex1- or xcex2-naphthyl, phenyl-C1-C6alkyl, xcex1- or xcex2-naphthyl-C1-C6alkyl, 5- or 6-membered heteroaryl or 5- or 6-membered heteroaryl-C1-C6alkyl, wherein those aromatic and heteroaromatic rings may be substituted by halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, nitro or by cyano; or
R4 and R5, together with the nitrogen atoms to which they are bonded, form a saturated or unsaturated 5- to 8-membered heterocyclic ring that 1) may be interrupted by oxygen, sulfur or by xe2x80x94NR14xe2x80x94 and/or may be substituted by halogen, C1-C10alkyl, C1-C10haloalkyl, hydroxy, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6haloalkoxy, mercapto, C1-C6alkylthio, C3-C7cycloalkyl, heteroaryl, heteroaryl-C1-C6alkyl, phenyl, phenyl-C1-C6alkyl or by benzyloxy, wherein the phenyl rings of the last three substituents may in turn be substituted by halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy or by nitro, and/or 2) may contain a fused or spiro-bound alkylene or alkenylene chain having from 2 to 6 carbon atoms that is optionally interrupted by oxygen or by sulfur, or at least one ring atom of the saturated or unsaturated heterocyclic ring bridges that alkylene or alkenylene chain; R14 is hydrogen, C1-C4alkyl, C1-C6alkylcarbonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or C3-C6alkynyl; and
G is hydrogen, a metal ion equivalent or an ammonium, sulfonium or phosphonium cation, which comprises reacting a compound of formula II: 
xe2x80x83wherein R0, R1, R2, R3 and n are as defined hereinbefore; R6 is R8R9Nxe2x80x94; R7is R10R11Nxe2x80x94 or R12Oxe2x80x94; and R8, R9, R10, R11 and R12 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6alkenyl or benzyl, wherein the phenyl ring of the benzyl group may be substituted by C1-C4alkyl, halogen, C1-C4haloalkyl, C1-C4alkoxy or by nitro, in an inert organic solvent, optionally in the presence of a base, with a compound of formula IV, IVa or IVb: 
xe2x80x83wherein R4 and R5 are as defined hereinbefore and Hexc2x7Hal is a hydrogen halide, and optionally converting the resulting compound of formula I wherein G is a metal ion equivalent or an ammonium cation, by salt conversion into the corresponding salt of formula I wherein G is a sulfonium or phosphonium cation, or by treatment with a Brxc3x6nsted acid into the corresponding compound of formula I wherein G is hydrogen.
The present invention relates also to the direct (xe2x80x98in situxe2x80x99) conversion, in a one-pot reaction, of compounds of formula I to compounds of formula Ia: 
wherein R0, R1, R2, R3, R4, R5 and n are as defined for formula I;
G0 is a group xe2x80x94C(O)xe2x80x94R30, xe2x80x94C(X1)xe2x80x94X2xe2x80x94R31, xe2x80x94C(X3)xe2x80x94N(R32)xe2x80x94R33, xe2x80x94SO2xe2x80x94R34 or xe2x80x94P(X4)(R35)xe2x80x94R36;
X1, X2, X3 and X4 are each independently of the others oxygen or sulfur;
R30 is unsubstituted or halo-substituted C1-C20alkyl, C2-C20alkenyl, C1-C8alkoxy-C1-C8alkyl, C1-C8alkylthio-C1-C8alkyl, poly-C1-C8alkoxy-C1-C8alkyl or unsubstituted or halo-, C1-C6alkyl- or C1-C6alkoxy-substituted C3-C8cycloalkyl, in which optionally at least one ring member has been replaced by oxygen and/or by sulfur, C3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or halo-, cyano-, nitro-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl-, C1-C6haloalkoxy-, C1-C6alkylthio- or C1-C6alkylsulfonyl-substituted phenyl, unsubstituted or halo-, nitro-, cyano-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl- or C1-C6haloalkoxy-substituted phenyl-C1-C6alkyl, unsubstituted or halo- or C1-C6alkyl-substituted heteroaryl, unsubstituted or halo- or C1-C6alkyl-substituted phenoxy-C1-C6alkyl, or unsubstituted or halo-, amino- or C1-C6alkyl-substituted heteroaryloxy-C1-C6alkyl;
R31 is unsubstituted or halo-substituted C1-C20alkyl, C2-C20alkenyl, C1-C8alkoxy-C2-C8alkyl, poly-C1-C8alkoxy-C2-C8alkyl, unsubstituted or halo-, C1-C6alkyl- or C1-C6alkoxy-substituted C3-C8cycloalkyl, C3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or halo-, cyano-, nitro-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl- or C1-C6haloalkoxy-substituted phenyl or benzyl;
R32 and R33 are each independently of the other hydrogen, unsubstituted or halo-substituted C1-C8alkyl, C3-C8cycloalkyl, C1-C8alkoxy, C3-C8alkenyl, C1-C8alkoxy-C1-C8alkyl, unsubstituted or halo-, C1-C8haloalkyl-, C1-C8alkyl- or C1-C8alkoxy-substituted phenyl or benzyl; or R32 and R33 together form a C3-C6alkylene chain in which a carbon atom has optionally been replaced by oxygen or by sulfur;
R34 is unsubstituted or halo-substituted C1-C8alkyl, C3-C8alkenyl, C3-C8haloalkenyl, C3-C8alkynyl, C3-C8haloalkynyl, or unsubstituted or halo-, C1-C6alkyl-, C1-C6alkoxy-, C1-C4haloalkyl-, C1-C4haloalkoxy-, cyano- or nitro-substituted phenyl or benzyl;
R35 and R36 are each independently of the other unsubstituted or halo-substituted C1-C8alkyl, C1-C8alkoxy, C1-C8alkylamino, di(C1-C8alkyl)amino, C1-C8alkylthio, C2-C8alkenylthio, C3-C7cycloalkylthio, or unsubstituted or halo-, nitro-, cyano-, C1-C4alkoxy-, C1-C4haloalkoxy-, C1-C4alkylthio-, C1-C4haloalkylthio-, C1-C4alkyl- or C1-C4haloalkyl-substituted phenyl, phenoxy or phenylthio,
which conversion comprises reacting compounds of formula I, optionally in the presence of an acid-binding agent or a catalyst, with an electrophile of formula XII or XIId:
G0xe2x80x94Lxe2x80x83xe2x80x83(XII) or
R32xe2x80x94Nxe2x95x90Cxe2x95x90X3xe2x80x83xe2x80x83(XIId),
xe2x80x83wherein G0, R32 and X3 are as defined hereinbefore except that R32 is not hydrogen, and L is a leaving group, for example R30C(O)Oxe2x80x94, R31X2xe2x80x94 or halogen, preferably chlorine, bromine or iodine.
Depending on the substituents R0 to R5, G and G0, the compounds of formulae I and Ia may be in the form of geometric and/or optical isomers or isomeric mixtures (atropisomers) and, when G is hydrogen, a metal ion equivalent, or an ammonium, sulfonium or phosphonium cation, they may be in the form of tautomers or tautomeric mixtures.
If the starting materials employed are not enantiomerically pure, the compounds of formulae I and Ia obtained in the above-described processes are generally in the form of racemates or diastereoisomeric mixtures which, if desired, can be separated on the basis of their physico-chemical properties according to known methods, such as, for example, fractional crystallisation following salt formation with optically pure bases, acids or metal complexes, or by chromatographic procedures, such as, for example, high-pressure liquid chromatography (HPLC) on acetyl cellulose.
In the present invention, the compounds of formulae I and Ia are to be understood as both the enriched and optically pure forms of the respective stereoisomers as well as the racemates and diastereoisomers. Unless there is specific reference to the individual optical antipodes, the given formulae are to be understood as the racemic mixtures that have been obtained by the preparation process according to the invention. When an aliphatic Cxe2x95x90C double bond is present, geometric isomerism may also occur.
The present invention relates also to the salts that the compounds of formulae I and Ia are able to form with acids. Suitable acids for the formation of the acid addition salt include both organic and inorganic acids. Examples of such acids are hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acids, sulfuric acid, acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, malonic acid, fumaric acid, organic sulfonic acids, lactic acid, tartaric acid, citric acid and salicylic acid.
In view of their acidity, the compounds of formula I wherein G is hydrogen can readily be converted in the presence of bases (proton acceptors) into the corresponding salts (wherein G is, for example, a metal ion equivalent or an ammonium cation), as described, for example, in EP-A-0 508 126. Any customary proton acceptor may be used as base. The salts are, for example, alkali metal salts, for example sodium and potassium salts; alkaline earth metal salts, for example calcium and magnesium salts; ammonium salts, that is to say, unsubstituted ammonium salts and mono- or poly-substituted ammonium salts, for example triethylammonium and methylammonium salts, or salts with other organic bases or other cations, for example sulfonium or phosphonium cations. Sulfonium cations include, for example, tri(C1-C4alkyl)sulfonium cations, which can be obtained from the corresponding alkali metal salts, for example, by salt conversion, for example using a cation exchanger.
Among the alkali metal and alkaline earth metal hydroxides as salt formers, special mention may be made, for example, of the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially the hydroxides of sodium and potassium. Suitable salt formers are described, for example, in WO 97/41112.
Examples of suitable amines for ammonium salt formation include both ammonia and primary, secondary and tertiary C1-C18alkylamines, C1-C4-hydroxyalkylamines and C2-C4alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four butylamine isomers, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylaminei octadecylamine, methyl-ethylamine, methyl-isopropylamine, methyl-hexylamine, methyl-nonylamine, methyl-pentadecylamine, methyl-octadecylamine, ethyl-butylamine, ethyl-heptylamine, ethyl-octylamine, hexyl-heptylamine, hexyl-octylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-2-amine, n-hexenyl-2-amine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, N-methylmorpholine, thiomorpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxy-anilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; but especially triethylamine, isopropylamine and diisopropylamine.
In the above definitions, halogen is to be undertstood as fluorine, chlorine, bromine or iodine, preferably fluorine, chorine or bromine.
The alkyl groups occurring in the substituent definitions are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, and the pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl isomers.
Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms. Haloalkyl is, for example, fluoromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, chloromethyl, dichloromethyl, dichlorofluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2-difluoroethyl, 2,2-dichloroethyl, 2,2,2-trichloroethyl or pentafluoroethyl, preferably trichloromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl or dichlorofluoromethyl.
Alkoxy groups preferably have a chain length of from 1 to 6 carbon atoms. Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tertbutoxy or a pentyloxy or hexyloxy isomer, preferably methoxy, ethoxy or n-propoxy.
Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trichloroethoxy.
There may be mentioned as examples of alkenyl radicals vinyl, allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl and 2-hexenyl; preferably alkenyl radicals having a chain length of from 3 to 6 carbon atoms.
There may be mentioned as examples of alkynyl radicals ethynyl, propargyl, 1-methyl-propargyl, 3-butynyl, but-2-yn-1-yl, 2-methylbut-3-yn-2-yl, but-3-yn-2-yl, 1-pentynyl, pent-4-yn-1-yl and 2-hexynyl; preferably alkynyl radicals having a chain length of from 3 to 6 carbon atoms.
Suitable haloalkenyl radicals include alkenyl groups substituted one or more times by halogen, halogen being in particular bromine or iodine and especially fluorine or chlorine, for example 2- and 3-fluoropropenyl, 2- and 3-chloropropenyl, 2- and 3-bromopropenyl, 2,2-di-fluoro-1-methylvinyl, 2,3,3-trifluoropropenyl, 3,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl, 4,4,4-trifluorobut-2-en-1-yl and 4,4,4-trichlorobut-2-en-1-yl. Preferred alkenyl radicals substituted once, twice or three times by halogen are those having a chain length of from 3 to 6 carbon atoms. The alkenyl groups may be substituted by halogen at saturated or unsaturated carbon atoms.
Suitable haloalkynyl groups include, for example, alkynyl groups substituted one or more times by halogen, halogen being bromine or iodine and especially fluorine or chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl and 4,4,4-trifluorobut-2-yn-1-yl.
Alkenyloxy is, for example, allyloxy, methallyloxy or but-2-en-1-yloxy.
Alkynyloxy is, for example, propargyloxy or 1-methylpropargyloxy.
Suitable haloalkenyloxy groups include alkenyloxy groups substituted one or more times by halogen, halogen being in particular bromine or iodine and especially fluorine or chlorine, for example 2- and 3-fluoropropenyloxy, 2- and 3-chloropropenyloxy, 2- and 3-bromopropenyloxy, 2,3,3-trifluoropropenyloxy, 2,3,3-trichloropropenyloxy, 4,4,4-trifluorobut-2-en-1-yloxy and 4,4,4-trichlorobut-2-en-1-yloxy.
Alkoxyalkyl groups have preferably from 1 to 6 carbon atoms. Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trichloroethoxy.
Polyalkoxy-alkyl is, for example, methoxymethoxy-methyl, ethoxymethoxy-methyl, ethoxy-ethoxy-methyl, n-propoxyethoxy-methyl, isopropoxyethoxy-methyl, methoxymethoxy-ethyl, ethoxymethoxy-ethyl, ethoxyethoxy-ethyl, n-propoxyethoxy-methyl, n-propoxyethoxy-ethyl, isopropoxyethoxy-methyl, isopropoxyethoxy-ethyl or (ethoxy)3-ethyl.
Suitable cycloalkyl substituents contain from 3 to 8 carbon atoms and are, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. They may be substituted one or more times by halogen, preferably fluorine, chlorine and/or bromine.
Alkylcarbonyl is especially acetyl or propionyl.
Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or a butoxycarbonyl, pentyloxycarbonyl or hexyloxycarbonyl isomer, preferably methoxycarbonyl or ethoxycarbonyl.
Phenyl, phenoxy and naphthyl may be in substituted form, in which case the substituents may, as desired, be in the ortho-, meta- and/or para-position and, in the case of the naphthyl ring system, in addition in the 5-, 6-, 7- and/or 8-position. Preferred positions for the substituents are the ortho- and para-position to the ring attachment point. Where the phenyl, phenoxy and naphthyl substituents are not explicitly mentioned they are, for example, C1-C4alkyl, halogen, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, nitro, cyano, amino, C1-C4alkylamino or di(C1-C4alkyl)amino.
Alkylthio groups preferably have a chain length of from 1 to 6 carbon atoms. Alkylthio is, for example, methylthio, ethylthio, propylthio, butylthio, pentylthio or hexylthio, or a branched isomer thereof, but is preferably methylthio or ethylthio.
Haloalkylthio is, for example, 2,2,2-trifluoroethylthio or 2,2,2-trichloroethylthio.
Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl; preferably methylsulfinyl or ethylsulfinyl.
Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
Alkylamino is, for example, methylamino, ethylamino, n-propylamino, isopropylamino or a butyl-, pentyl- or hexyl-amine isomer.
Dialkylamino is, for example, dimethylamino, methylethylamino, diethylamino, n-propylmethylamino, dibutylamino or diisopropylamino.
Alkylthioalkyl is, for example, methylthiomethyl, methylthioethyl, ethylthiomethyl, ethylthioethyl, n-propylthiomethyl, n-propylthioethyl, isopropylthiomethyl or isopropylthioethyl.
Heterocyclyl radicals are preferably 4- to 8-membered rings that contain 1 or 2 hetero atoms, for example N, S and/or O. They are usually saturated.
Heteroaryl radicals are usually 5- or 6-membered aromatic heterocycles that contain preferably from 1 to 3 hetero atoms, such as N, S and/or O. The following are examples of suitable heterocyclyl and heteroaryl radicals: pyridyl, pyrrolidyl, piperidyl, pyranyl, dioxanyl, azetidyl, oxetanyl, pyrimidyl, triazinyl, thiazolyl, triazolyl, thiadiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazinyl, furyl, thienyl, morpholyl, piperazinyl, pyrazolyl, benzoxazolyl, benzothiazolyl, quinoxalyl, indolyl and quinolyl. Those heterocycles and heteroaromatic radicals may in addition be substituted, the substituents, where they are not explicitly mentioned, being, for example, halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, C1-C6alkylthio, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, phenyl, nitro or cyano.
The substituent definition according to which xe2x80x9cR4 and R5, together with the nitrogen atoms to which they are bonded, form a saturated or unsaturated, 5- to 8-membered heterocyclic ring that 1) may be interrupted by oxygen, sulfur or by xe2x80x94NR14xe2x80x94 and/or may be substituted by halogen, C1-C10alkyl, C1-C10haloalkyl, hydroxy, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6haloalkoxy, mercapto, C1-C6alkylthio, C3-C7cyploalkyl, heteroaryl, heteroaryl-C1-C6alkyl, phenyl, phenyl-C1-C6alkyl or by benzyloxy, wherein the phenyl rings of the last three substituents may in turn be substituted by halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy or by nitro, and/or 2) may contain a fused or spiro-bound alkylene or alkenylene chain having from 2 to 6 carbon atoms that is optionally interrupted by oxygen or by sulfur, or at least one ring atom of the saturated or unsaturated heterocyclic ring bridges that alkylene or alkenylene chainxe2x80x9d, signifies, for example, the following heterocyclic ring systems: 
In the above polycyclic rings systems, the abbreviated representation 
denotes the group 
The 5- to 8-membered heterocyclic rings that the substituents R4 and R5 together may form and the fused or spiro-bound alkylene or alkenylene chains having from 2 to 6 carbon atoms may accordingly be interrupted once or twice by hetero atoms, such as, for example, oxygen.
Meanings corresponding to those given hereinbefore can also be ascribed to the substituents in composite definitions, such as, for example, alkoxy-alkoxy, alkylsulfonylamino, alkyl-aminosulfonyl, alkoxy-carbonyl, alkyl-carbonylamino, phenyl-alkyl, naphthyl-alkyl and heteroaryl-alkyl.
In the definitions of alkylcarbonyl, alkylcarbonylamino and alkoxycarbonyl, the carbon atom of the carbonyl is not included in the lower and upper limits given for the number of carbon atoms in each particular case.
The composite definitions that may arise in respect of the radicals R30, R3, and R34 in substituent G0 in formula Ia, such as, for example, cycloalkyl-thio, cycloalkyl-alkyl, heterocyclyl-alkyl, heteroaryl-alkyl, phenyl-alkyl, phenoxy-alkyl and heteroaryloxy-alkyl radicals, are derived from the corresponding radicals of the radicals mentioned above. Heterocyclyl radicals are preferably those containing 1 or 2 hetero atoms, such as, for example, N, S and O. They are usually saturated.
Heteroaryl radicals are usually aromatic heterocycles that contain preferably from 1 to 3 hetero atoms, such as N, S and/or O. Such heterocycles and heteroaromatic radicals may furthermore be substituted, for example by halogen, C1-C4alkyl and/or amino. The C2-C20alkenyl groups represented by R31 may be mono- or poly-unsaturated. They contain preferably from 2 to 12, especially from 2 to 6, carbon atoms.
The definition of the electrophile Gxe2x80x94L of formula XII includes the following electrophiles: Lxe2x80x94C(O)xe2x80x94R30 (XIIa), Lxe2x80x94C(X1)xe2x80x94X2xe2x80x94R31 (XIIb), Lxe2x80x94C(X3)xe2x80x94N(R32)xe2x80x94R33 (XIIc), R32Nxe2x95x90Cxe2x95x90X3(XIId), Lxe2x80x94SO2xe2x80x94R34 (XIIe) and Lxe2x80x94P(X4)(R35)xe2x80x94R36 (XIIf).
In the electrophile of formula XII, L is a leaving group, such as, for example, R30C(O)Oxe2x80x94 or R31Oxe2x80x94 (wherein R30 and R3 are as defined for formula Ia), or halogen, preferably chlorine, bromine or iodine.
The process according to the invention is especially well suited to the preparation of compounds of formula I wherein R0 is, each independently of any other, halogen, C1-C6alkyl, C1-C6haloalkyl, hydroxy, C1-C6alkoxy, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylsulfonylamino, C1-C6alkylaminosulfonyl, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl or carboxy; and
R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C10alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, C1-C6alkoxy-C1-C6alkoxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, nitro, amino, C1-C4alkylamino or di(C1-C4alkyl)amino.
The process according to the invention is especially well suited also to the preparation of compounds of formula I wherein R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4haloalkyl, C3- or C4-haloalkenyl, C3-C6cycloalkyl, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C4alkoxy, C3- or C4-alkenyloxy, C3- or C4-alkynyloxy, C1-C4haloalkoxy, nitro or amino.
The process according to the invention is especially well suited also to the preparation of compounds of formula I wherein R4 and R5, together with the nitrogen atoms to which they are bonded, form a saturated or unsaturated, 6- or 7-membered heterocyclic ring that 1) may be interrupted once by oxygen or by sulfur and/or 2) may contain a fused or spiro-bound alkylene chain having from 2 to 5 carbon atoms that is optionally interrupted once or twice by oxygen or by sulfur, or at least one ring atom of the saturated or unsaturated heterocyclic ring bridges that alkylene chain.
In a preferred variant of the process according to the invention, there are preferably used compounds of formula II wherein R8, R9, R10, R11 and R12 are hydrogen, C1-C6alkyl or benzyl.
The preparation of the compounds of formulae I and Ia is explained in detail in the following Reaction Schemes 1 and 2. 
The compounds of formulae 11 and IV, IVa or IVb can be used in equimolar amounts, but an excess of from 5 to 50 mol % of the compound of formula IV, IVa or IVb can be of advantage.
The reaction of compounds of formula II with compounds of formula IV, IVa or IVb is carried out at a reaction temperature of from 0xc2x0 to 200xc2x0 C., a temperature range of from 80xc2x0 C. to 150xc2x0 C. being preferred.
Suitable inert organic solvents for the reaction of compounds of formula II with compounds of formula IV, IVa or IVb are, for example, aromatic, aliphatic and cycloaliphatic hydrocarbons, for example, benzene, toluene, the xylene isomers ortho-, meta- and para-xylene, cyclohexane and methylcyclohexane; halogenated hydrocarbons, for example chlorobenzene and the dichlorobenzene isomers 1,2-, 1,3- and 1,4-dichlorobenzene; ethers, for example dibutyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane (DME), ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, 1,3-dioxolane and dioxane; nitrites, for example acetonitrile, propionitrile and benzonitrile; dialkyl sulfoxides, for example dimethyl sulfoxide (DMSO); amides and lactams, for example N,N-dimethylformamide (DMF), N,N-diethylformamide and N-methylpyrrolidone (NMP); alcohols, glycols (diols) and polyalcohols, for example propanol, butanol, cyclohexanol, ethylene glycol and 2-ethoxyethanol, and also, generally, carboxylic acids, for example acetic acid and propionic acid, or mixtures of those solvents.
Preference is given to those organic solvents having a boiling point xe2x89xa780xc2x0 C., especially a boiling point xe2x89xa7100xc2x0 C.
Special preference is given to toluene, the xylene isomers ortho-, meta- and para-xylene, methylcyclohexane, chlorobenzene and the dichlorobenzene isomers 1,2-, 1,3- and 1,4-dichlorobenzene.
The reaction according to the invention is preferably carried out in an inert gas atmosphere, for example in a nitrogen or argon gas atmosphere.
The condensation of compounds of formula II with compounds of formula IV can be carried out with or without the addition of a base. The same condensation reaction carried out with compounds of formula IVa or IVb (instead of compounds of formula IV) is advantageously carried out in the presence of a base. Suitable bases in that case include, for example, nitrogen bases generally, for example tertiary amines and pyridines, for example C1-C6trialkylamines, quinuclidine and 4-dimethylaminopyridine. Further suitable bases are, for example, alkali metal alcoholates, for example sodium and potassium methanolate, sodium and potassium ethanolate and sodium and potassium tert-butanolate. It is also possible to use inorganic bases, for example alkali metal and alkaline earth metal hydrides, such as sodium, potassium or calcium hydride, hydroxides, such as sodium or potassium hydroxide, carbonates, such as sodium or potassium carbonate, and hydrogen carbonates, such as sodium or potassium hydrogen carbonate, especially in the form of solutions in alcohol. Such bases are used in catalytic amounts or in a molar excess of up to 5 based on the compound of formula II.
In a preferred embodiment of the process according to the invention, an aromatic hydrocarbon having a boiling point  greater than 80xc2x0 C., for example xylene, is used as the reaction medium in which the reactants of formulae II and IV, IVa or IVb are dissolved. Preferably, the compound of formula IV, IVa or IVb is used in an excess of from 5 to 20 mol % based on the compound of formula II. The reaction mixture is heated at reflux temperature for from 1 to 3 hours in an inert gas atmosphere, with or without the addition of a base when a compound of. formula IV is used, and in the presence of an equimolar amount or an up to 5-fold excess of an organic base, such as triethylamine, when a compound of formula IVa or IVb is used. After cooling and the addition of dilute acid, the desired product (G=hydrogen) precipitates in the form of a crystalline solid and can be filtered off directly and washed with a suitable washing agent, for example water and/or hexane.
The compounds of formula I wherein R0, R1, R2, R3, R4, R5 and n are as defined hereinbefore and G is hydrogen, a metal ion equivalent or an ammonium cation can readily be converted into the compounds of formula Ia either
a) in accordance with the invention, directly in the reaction solution in a one-pot reaction, without isolation, or
b) in a subsequent reaction step, after having been isolated, by means of reaction, optionally in the presence of an acid-binding agent or a catalyst, with an electrophile of formula XII wherein G0 is as defined hereinbefore and L is a leaving group, for example R30C(O)Oxe2x80x94 or R31Oxe2x80x94 (wherein R30 and R31, are as defined for formula Ia), or halogen, preferably chlorine, bromine or iodine. Reaction Scheme 2 illustrates that derivatisation step. 
The acid-binding agents that may be used for the reaction of a compound of formula I with an electrophile of formula XII may be conventional proton acceptors, for example alkali metal hydrides, alkali metal alcoholates, alkali metal or alkaline earth metal carbonates or hydrogen carbonates, or nitrogen bases generally, for example triethylamine, diisopropylamine, pyridine, quinoline, diazabicyclononene (DBN) and diazabicycloundecene (DBU). There may be added as catalysts for the reaction of a compound of formula I with an electrophile of formula lid catalysts that accelerate the reaction, for example organotin compounds, for example dibutyltin dilaurate.
The solvents used may be any that are inert with respect to the electrophiles of formulae XII and XIIa to XIIf, for example aromatic hydrocarbons, for example benzene, toluene or a xylene isomer; halogenated hydrocarbons, for example dichloromethane, trichloromethane, chlorobenzene or a dichlorobenzene isomer; amides, for example N,N-dimethylformamide (DMF) or 1-methyl-2-pyrrolidone (NMP); or ethers, for example dibutyl ether, 1,2-dimethoxyethane (DME), 1,3-dioxolane, tetrahydrofuran or dioxane.
Analogous reactions of compounds of formula I wherein G is hydrogen in accordance with the above variant b), that is to say, as a separate reaction step, are described, for example, in WO 97/02243 and EP-A-0 508 126.
The compounds of formula I prepared in accordance with the invention wherein G is hydrogen, a metal ion equivalent or an ammonium, sulfonium or phosphonium cation are therefore used especially as starting compounds for the xe2x80x98in situxe2x80x99 preparation of compounds of formula Ia wherein G0 is a group xe2x80x94C(O)xe2x80x94R30, xe2x80x94C(X1)xe2x80x94X2xe2x80x94R31, xe2x80x94C(X3)xe2x80x94N(R32)xe2x80x94R33, xe2x80x94SO2xe2x80x94R34 or xe2x80x94P(X4)(R35)xe2x80x94R36; and R30, R31, R32, R33, R34, R35, R36, X1, X2, X3 an X4 are as defined for formula Ia.
The compounds of formula I: 
wherein R0 is, each independently of any other, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, cyano-C1-C6alkyl, C2-C6haloalkenyl, cyano-C2-C6alkenyl, C2-C6haloalkynyl, cyano-C2-C6alkynyl, hydroxy, hydroxy-C1-C6alkyl, C1-C6alkoxy, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylsulfonylamino, C1-C6alkylaminosulfonyl, C1-C6alkylcarbonyl, C1-C6alkylcarbonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl-C2-C6alkenyl, C1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or an aromatic ring that contains 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the latter two aromatic rings may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro; or R0, together with the adjacent substituents R1, R2 and R3, forms a saturated or unsaturated C3-C6hydrocarbon bridge that may be interrupted by 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and/or may be substituted by C1-C4alkyl; R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl, C2-C6haloalkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkylcarbonyl-C2-C6alkynyl, cyano-C2-C6alkynyl, nitro-C2-C6alkynyl, C3-C6-halocycloalkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C10alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, C1-C6alkoxy-C1-C6alkoxy, mercapto, C1-C6alkylthio, C1-C6halolkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino or phenoxy in which the phenyl ring may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro;
R2 also may be phenyl, naphthyl or a 5- or 6-membered aromatic ring that may contain 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halogen, C3-C8cycloalkyl, hydroxy, mercapto, amino, cyano, nitro or by formyl; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsultinyl, C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl-(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl, mono- or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or by C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halo-substituted C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkyls C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl-(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl, mono- or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by a radical of the formula COOR50, CONR51, SO2NR53R54 or SO2OR55 wherein R50, R51, R52, R53, R54 and R5 are each independently of the others C1-C6alkyl, C2-C6alkeny or C3-C6alkynyl or halo-, hydroxy-, alkoxy-, mercapto-, amino-, cyano-, nitro-, alkylthio-, alkyl-sulfinyl- or alkylsulfonyl-substituted C1-C6alkyl, C2-C6alkenyl or C3-C6alkynyl; n is 1 or 2; R4 and R5, together with the nitrogen atoms to which they are bonded, form a saturated or unsaturated 5- to 8-membered heterocyclic ring that 1) is interrupted by oxygen, sulfur or by xe2x80x94NR14xe2x80x94 and may be substituted by halogen, C1-C10alkyl, C1-C10haloalkyl, hydroxy, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6haloalkoxy, mercapto, C1-C6alkylthio, C3-C7cycloalkyl, heteroaryl, heteroaryl-C1-C6alkyl, phenyl, phenyl-C1-C6alkyl or by benzyloxy, wherein the phenyl rings of the last three substituents may in turn be substituted by halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy or by nitro, and 2) may contain a fused or spiro-bound alkylene or alkenylene chain having from 2 to 6 carbon atoms that is optionally interrupted by oxygen or by sulfur, or at least one ring atom of the saturated or unsaturated heterocyclic ring bridges that alkylene or alkenylene chain; R14 is hydrogen, C1-C4alkyl, C1-C6alkylcarbonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or C3-C6alkynyl; and G is hydrogen or a metal ion equivalent or an ammonium, sulfonium or phosphonium cation, are new. The present invention accordingly relates also to those compounds.
The compounds of formula Ia 
wherein R0 is, each independently of any other, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, cyano-C1-C6alkyl, C2-C6haloalkenyl, cyano-C2-C6alkenyl, C2-C6haloalkynyl, cyano-C2-C6alkynyl, hydroxy, hydroxy-C1-C6alkyl, C1-C6alkoxy, nitro, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylsulfonylamino, C1-C6alkylaminosulfonyl, C1-C6alkylcarbonyl, C1-C6alkylcarbonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl-C2-C6alkenyl, C1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or an aromatic ring that contains 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the latter two aromatic rings may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro; or R0, together with the adjacent substituents R1, R2 and R3, forms a saturated or unsaturated C3-C6hydrocarbon bridge that may be interrupted by 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and/or may be substituted by C1-C4alkyl; R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C1-C6alkoxycarbbnyl-C2-C6alkenyl, C1-C6alkylcarbonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl, C2-C6haloalkynyl, C1-C6alkoxycarbonyl-C2-C6alkynyl, C1-C6alkylcarbonyl-C2-C6alkynyl, cyano-C2-C6alkynyl, nitro-C2-C6alkynyl, C3-C6halocycloalkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, C1-C6alkoxy-C1-C6alkoxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, nitro, amino, C1-C6alkylamino, di-(C1-C6alkyl)amino or phenoxy in which the phenyl ring may be substituted by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro;
R2 also may be phenyl, naphthyl or a 5- or 6-membered aromatic ring that may contain 1 or 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halogen, C3-C8cycloalkyl, hydroxy, mercapto, amino, cyano, nitro or by formyl; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6-alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl-(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenyl-sulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl, mono- or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or by C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by halo-substituted C1-C6alkyl, C1-C6alkoxy, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, mono-C1-C6alkylamino, di(C1-C6alkyl)amino, C1-C6alkylcarbonylamino, C1-C6alkylcarbonyl(C1-C6alkyl)amino, C2-C6alkenyl, C3-C6alkenyloxy, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenyloxy, C2-C6alkenylcarbonyl, C2-C6alkenylthio, C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, mono- or di-(C2-C6alkenyl)amino, C1-C6alkyl-(C3-C6alkenyl)amino, C2-C6alkenylcarbonylamino, C2-C6alkenylcarbonyl(C1-C6alkyl)amino, C2-C6alkynyl, C3-C6alkynyloxy, hydroxy-C3-C6alkynyl, C1-C6alkoxy-C3-C6alkynyl, C1-C6alkoxy-C4-C6alkynyloxy, C2-C6alkynylcarbonyl, C2-C6alkynylthio, C2-C6alkynylsulfinyl, C2-C6alkynylsulfonyl, mono- or di-(C3-C6alkynyl)amino, C1-C6alkyl(C3-C6alkynyl)amino, C2-C6alkynylcarbonylamino or C2-C6alkynylcarbonyl(C1-C6alkyl)amino; and/or
the phenyl ring, the naphthyl ring system and the 5- or 6-membered aromatic ring may be substituted by a radical of the formula COOR50, CONR51, SO2NR53R54 or SO2OR55 wherein R50, R51, R52, R53, R54 and R55 are each independently of the others C1-C6alkyl, C2-C6alkenyl or C3-C6alkynyl or halo-, hydroxy-, alkoxy-, mercapto-, amino-, cyano-, nitro-, alkylthio-, alkylsulfinyl- or alkylsulfonyl-substituted C1-C6alkyl, C2-C6alkenyl or C3-C6alkynyl;
n is 1 or 2;
R4 and R5, together with the nitrogen atoms to which they are bonded, form a saturated or unsaturated 5- to 8-membered heterocyclic ring that 1) is interrupted by oxygen, sulfur or by xe2x80x94NR14xe2x80x94 and may be substituted by halogen, C1-C10alkyl, C1-C10haloalkyl, hydroxy, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6haloalkoxy, mercapto, C1-C6alkylthio, C3-C7Cycloalkyl, heteroaryl, heteroaryl-C1-C6alkyl, phenyl, phenyl-C1-C6alkyl or by benzyloxy, wherein the phenyl rings of the last three substituents may in turn by substituted by halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyl C1-C6haloalkoxy or by nitro, and 2) may contain a fused or spiro-bound alkylene or alkenylene chain having from 2 to 6 carbon atoms that is optionally interrupted by oxygen or by sulfur, or at least one ring atom of the saturated or unsaturated heterocyclic ring bridges that alkylene or alkenylene chain; R14 is hydrogen, C1-C4alkyl, C1-C6alkylcarbonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or C3-C6alkynyl; and G0 is a group xe2x80x94C(O)xe2x80x94R30, xe2x80x94C(X1)xe2x80x94X2xe2x80x94R31 or xe2x80x94SO2xe2x80x94R34;
X1, X2, X3 and X4 are each independently of the others oxygen or sulfur; R30 is unsubstituted or halo-substituted C1-C20alkyl, C2-C20alkenyl, C1-C8alkoxy-C1-C6alkyl, C1-C8alkylthio-C1-C8alkyl, poly-C1-C8alkoxy-C1-C8alkyl or unsubstituted or halo-substituted C3-C8cycloalkyl, C3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or halo-, cyano-, nitro-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl-, C1-C6haloalkoxy-, C1-C6alkylthio- or C1-C6alkylsulfonyl-substituted phenyl, unsubstituted or halo-, nitro-, cyano-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl- or C1-C6haloalkoxy-substituted phenyl-C1-C6alkyl, unsubstituted or halo- or C1-C6alkyl-substituted heteroaryl, unsubstituted or halo- or C1-C6alkyl-substituted phenoxy-C1-C6alkyl, or unsubstituted or halo-, amino- or C1-C6alkyl-substituted heteroaryloxy-C1-C6alkyl; R31 is unsubstituted or halo-substituted C1-C20alkyl, C2-C20alkenyl, C1-C8alkoxy-C2-C8alkyl, poly-C1-C8alkoxy-C2-C8alkyl, unsubstituted or halo- or C1-C6alkoxy-substituted C3-C8cycloalkyl, C3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or halo-, cyano-, nitro-, C1-C6alkyl-, C1-C6alkoxy-, C1-C6haloalkyl- or C1-C6haloalkoxy-substituted phenyl or benzyl; and R34 is unsubstituted or halo-substituted C1-C8alkyl, or unsubstituted or halo-, C1-C6alkyl-, C1-C6alkoxy-, C1-C4haloalkyl-, C1-C4haloalkoxy-, cyano- or nitro-substituted phenyl, are new. The present invention accordingly relates also to those compounds.
The compounds of formula II: 
wherein R0, R1, R2, R3, R6, R7 and n are as defined hereinbefore are new and were developed especially for the process according to the invention. The present invention accordingly relates also to those compounds.
Preferred compounds of formula II are those wherein R1, R2 and R3 are each independently of the others hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C3-C6cycloalkyl, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, hydroxy, C1-C4alkoxy, C3- or C4-alkenyloxy, C3- or C4-alkynyloxy, C1-C4haloalkoxy, nitro or amino.
Preference is given also to compounds of formula II wherein R1 is C2-C6alkyl.
Likewise preferred are compounds of formula II wherein n is O.
Of those, special preference is given to compounds of formula II wherein R1 is C2-C4alkyl, C1-C4alkoxy, C2-C4alkynyl or C3-C6cycloalkyl and R3 is C1-C4alkyl, C1-C4alkoxy, C2-C4alkynyl or C3-C6cycloalkyl.
Likewise preferred are compounds of formula II wherein R1 is C2-C6alkynyl.
Preference is given to those compounds of formula II wherein R1 and R3 are each independently of the other C2-C6alkyl, C2-C6alkynyl, C1-C10Dalkoxy or C3-C6cycloalkyl. Of those, special preference is given to the compounds wherein R1 is C2-C6alkyl and R3 is C2-C6alkyl, C2-C6alkynyl or C1-C10alkoxy.
Also important are the compounds of formula II wherein R6 is R8R9Nxe2x80x94 and R7 is R10R11Nxe2x80x94; R8, R9, R10and R11, being as defined for formula II.
The compounds of formula IIa 
wherein R0, R1, R2, R3 and n are as defined for formula II and R8, R9, R10and R11 are hydrogen, can be obtained, for example, directly from the corresponding phenylmalonic acid dinitriles of formula VI: 
wherein R0, R1, R2, R3 and n are as defined hereinbefore, by means of hydrolysis. Concentrated mineral acids, for example, sulfuric acid or nitric acid, are suitable as hydrolysing agents, where appropriate with the addition of water.
The compounds of formula IIa: 
wherein R0, R1, R2, R3 and n are as defined for formula I and R8, R9, R10 and R11 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6alkenyl or benzyl, wherein the phenyl ring of the benzyl group may be substituted by C1-C4alkyl, halogen, C1-C4haloalkyl, C1-C4alkoxy or by nitro, can be prepared, for example, as follows:
1) a phenyl acetamide of formula VII: 
wherein R0, R1, R2, R3, R8, R9 and n are as defined hereinbefore, is either
a) reacted with an isocyanate of formula XI:
R10Nxe2x95x90Cxe2x95x90Oxe2x80x83xe2x80x83(XI),
xe2x80x83wherein R10 is as defined hereinbefore except that R10 is not hydrogen, the reaction being optionally catalysed by a base and carried out in an inert reaction medium, (R11xe2x95x90hydrogen in the compound of formula IIa), or
b) reacted at reflux temperature with a carbonate of formula XIV: 
xe2x80x83wherein R12 is C1-C6alkyl, C1-C6haloalkyl, C3-C6alkenyl or benzyl, wherein the phenyl ring of the benzyl group may be substituted by C1-C4alkyl, halogen, C1-C4haloalkyl, C1-C4alkoxy or by nitro, and the compound of formula IIb: 
xe2x80x83wherein R0, R1, R2, R3, R8, R9, R12 and n are as defined hereinbefore, is obtained initially and that compound is then reacted in an inert solvent with an amine of formula X:
R10R11NHxe2x80x83xe2x80x83(X),
xe2x80x83wherein R10 and R11 are as defined hereinbefore, or
2) a phenylacetic acid ester of formula VIII: 
xe2x80x83wherein R0, R1, R2, R3, R12 and n are as defined hereinbefore, is either
c) reacted with an isocyanate of formula XV:
R8Nxe2x95x90Cxe2x95x90Oxe2x80x83xe2x80x83(XV),
xe2x80x83wherein R8 is as defined hereinbefore except that R8 is not hydrogen, the reaction being optionally catalysed by a base and carried out in an inert reaction medium, and the compound of formula IIb: 
xe2x80x83wherein R0, R1, R2, R3, R8, R12 and n are as defined hereinbefore and R9 is hydrogen, is obtained initially, and that compound is then reacted in an inert solvent, in the manner described under 1) b), with an amine of formula X, or
d) reacted with a carbonate of formula XVI 
xe2x80x83wherein R13 has the same meanings as R12, at elevated temperature, and a phenylmalonic acid diester of formula III: 
xe2x80x83wherein R0, R1, R2, R3, R12, R13 and n are as defined hereinbefore, is obtained initially and that compound is then reacted in an inert solvent, in a manner analogous to that described under 1) b), with an amine of formula IX or X:
R8R9NHxe2x80x83xe2x80x83(IX) or
R10R11NHxe2x80x83xe2x80x83(X),
xe2x80x83wherein R8, R9, R10 and R11 are as defined hereinbefore.
The above process variants are illustrated in the following Reaction Scheme 3. 
The phenylmalonic acid diamides of formula IIa can be obtained in accordance with Reaction Scheme 3 (variant a)), according to known standard procedures, from phenyl acetamides of formula VII using the isocyanates of formula XI, the reaction being optionally catalysed by a base and carried out in an inert solvent.
According to Reaction Scheme 3 (variant b)), the phenylmalonic acid diamides of formula IIa can be obtained from the phenyl acetamides of formula VVI also by heating for several hours at reflux temperature in carbonates of formula XIV as solvents, via compounds of formula IIb and with subsequent amidation in a solvent using amines of formula X. Analogous reactions with phenylacetic acid ester derivatives and carbonates of formula XVI are described, for example, in WO 97/02243.
Further alternative processes for the preparation of the phenylmalonic acid diamides of formula IIa, which start from the phenylacetic acid esters of formula VIII, are provided according to Reaction Scheme 3 by the following two process variants: according to variant c), the compounds of formula VIII can, for example, first of all be reacted analogously to Tetrahedron Lett. 1974, 2427 with isocyanates of formula XV, the reaction being catalysed by a base and carried out in an inert reaction medium, to form the compounds of formula IIb (R9=hydrogen), which are then amidated in an inert solvent in a manner analogous to variant b) using amines of formula X; or, according to variant d), the compounds of formula VIII can, for example, first of all be reacted at reflux temperature, in carbonates of formula XVI as solvents, to form the phenylmalonic acid diesters of formula II, which are then amidated in a solvent in a manner analogous to variant b) using amines of formula IX or X.
The compounds of formulae IV, IVa and IVb are either known or can be prepared analogously to known procedures. Processes for the preparation of compounds of formula IV are described, for example, in WO 95/00521 and PCT/EP Application number 99/01593.
The phenylmalonic acid dinitrile derivatives of formula VI are either known or can be prepared analogously to known procedures as described, for example, in Chem. Commun. 1984, 932 or J. Am. Chem. Soc. 121, 1473 (1999).
The phenyl acetamides and phenylacetic acid esters of formulae VII and VIII are known. Phenylacetic acid esters of formula VIII are described, for example, in WO 97/02243.
The reagents of formulae IX, X, XI, XII and XIIa, XIIb, XIIc, XIId, XIIe and XIIf, XIV, XV and XVI used in Reaction Schemes 1, 2 and 3, respectively, are either known or can be prepared analogously to known procedures.
The present process is distinguished by:
a) easy accessibility of the starting compounds of formula II,
b) simple reaction procedure and working up,
c) generally high product yields,
d) an economically and ecologically advantageous one-pot process for further derivatisation of the compounds of formula I to produce compounds of formula Ia (e.g. conversion of substituent G to G0), and
e) its economic and ecological advantages derived from the fact that the individual process steps, starting from the preparation of the compounds of formula II (Reaction Scheme 3), the reaction thereof with compounds of formula IV, IVa or IVb to form compounds of formula I (Reaction Scheme 1) and the reaction thereof with electrophiles of formula XII, XIIa, XIIb, XIIc or XIId, can be used for a continuous reaction procedure for the preparation of compounds of formula Ia.
The present preparation process is suitable also especially for the large-scale preparation of 4-aryl-5-oxopyrazoline derivatives of formulae I and Ia.